Growth Hormone/Insulin-Like Growth Factor-1 Axis as Related to Body Mass Index in Patients with Idiopathic Short Stature

OBJECTIVE Idiopathic short stature (ISS) is a heterogeneous disorder. An impairment of growth hormone (GH)/insulin-like growth factor 1 (IGF-1)/IGF-1 receptor (IGF-1 R) axis is postulated. To evaluate the somatotropic axis in relation to body mass index (BMI), serum IGF-1, IGF-binding protein-3 (IGFBP-3) and the expression of IGF-1 R genes in patients with ISS. METHODS Fifty-five ISS patients (24 F/31 M) aged 14.6 ± 5.5 years (range 3.5-28.5 years) and 25 BMI- and pubertal stage-matched peers were enrolled in the study. The ISS patients underwent a four-day standard GH stimulation test to evaluate IGF-1 generation. mRNA expression of the IGF-1 R gene in peripheral blood leukocytes was evaluated. ISS patients and controls were compared with respect to anthropometric and laboratory data. The results were also analyzed after subdividing the two groups into low-normal [BMI standard deviation score (SDS) between -2 to -1)] and normal (BMI SDS between -1 to +1) BMI subgroups. RESULTS Basal serum IGF-1 concentrations were lower in ISS subjects compared to controls who had similar BMI SDS values (p=0.000). Subgroup analyses revealed that there were no significant differences between low-normal BMI ISS subjects and low-normal BMI controls with respect to serum IGF-1 and IGFBP-3 concentrations. However, in the normal BMI ISS subgroup, basal and stimulated IGF-1 levels were significantly lower than the basal values in their control counterparts (basal: p=0.000; stimulated: p=0.007). mRNA expression of IGF-1 R gene was not found to be significantly different in ISS subjects and controls. CONCLUSIONS ISS patients were found to have lower IGF-1 concentrations than BMI-matched peers, a finding supporting presence of an impairment in the somatotropic axis. IGF-1 R expression does not seem to be impaired in ISS patients. ISS patients with low-normal BMI SDS also tend to display a relative IGF-1 resistance, whereas those with normal BMI SDS tend to be less GH-sensitive than healthy peers.